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Chlamydia inhibits progesterone receptor mRNA expression in SHT-290 cells.

ABSTRACT: Chlamydia trachomatis is the most commonly diagnosed sexually transmitted infection in the UK, with over 200,000 positive diagnoses annually. The infection is thought to cause reproductive complications including problems in conceiving a pregnancy through to miscarriage and early or stillbirth. One potential reason Chlamydia may impact upon pregnancy is through disrupting the embryo implantation at the earliest stages of pregnancy is by altering the ability of specific cells that line the uterus called stromal cells to respond to the hormone progesterone, the hormone responsible for preparing the uterus for pregnancy. The results of this study showed that Chlamydial infection of these uterus lining stromal cells decreased the levels of specific progesterone sensitive markers which are associated with early embryo implantation, suggesting a loss of responsiveness to progesterone treatment. These changes were accompanied by a decrease in the levels of RNA for the progesterone receptor which is responsible for progesterone activity, suggesting that this is a potential mechanism through which Chlamydia could directly inhibit the effects of progesterone on uterine cells.

SUBMITTER: Brown M

PROVIDER: S-EPMC8812455 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Chlamydia inhibits progesterone receptor mRNA expression in SHT-290 cells.

Brown Megan M Rae Mick M Wheelhouse Nick N

Reproduction & fertility 20210101 1

<i>Chlamydia trachomatis</i> is the most commonly diagnosed sexually transmitted infection in the UK, with over 200,000 positive diagnoses annually. The infection is thought to cause reproductive complications including problems in conceiving a pregnancy through to miscarriage and early or stillbirth. One potential reason Chlamydia may impact upon pregnancy is through disrupting the embryo implantation at the earliest stages of pregnancy is by altering the ability of specific cells that line the ...[more]

PMID: 35128439

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Project description:BackgroundMifepristone (MF) has been largely used in reproductive medicine due to its capacity to modulate the progesterone receptor (PR). The study of MF has been expanded to the field of oncology; yet it remains unclear whether the expression of PR is required for MF to act as an anti-cancer agent. Our laboratory has shown that MF is a potent inhibitor of ovarian cancer cell growth. In this study we questioned whether the growth inhibitory properties of MF observed in ovarian cancer cells would translate to other cancers of reproductive and non-reproductive origin and, importantly, whether its efficacy is related to the expression of cognate PR.MethodsDose-response experiments were conducted with cancer cell lines of the nervous system, breast, prostate, ovary, and bone. Cultures were exposed to vehicle or increasing concentrations of MF for 72 h and analysed for cell number and cell cycle traverse, and hypodiploid DNA content characteristic of apoptotic cell death. For all cell lines, expression of steroid hormone receptors upon treatment with vehicle or cytostatic doses of MF for 24 h was studied by Western blot, whereas the activity of the G1/S regulatory protein Cdk2 in both treatment groups was monitored in vitro by the capacity of Cdk2 to phosphorylate histone H1.ResultsMF growth inhibited all cancer cell lines regardless of tissue of origin and hormone responsiveness, and reduced the activity of Cdk2. Cancer cells in which MF induced G1 growth arrest were less susceptible to lethality in the presence of high concentrations of MF, when compared to cancer cells that did not accumulate in G1. While all cancer cell lines were growth inhibited by MF, only the breast cancer MCF-7 cells expressed cognate PR.ConclusionsAntiprogestin MF inhibits the growth of different cancer cell lines with a cytostatic effect at lower concentrations in association with a decline in the activity of the cell cycle regulatory protein Cdk2, and apoptotic lethality at higher doses in association with increased hypodiploid DNA content. Contrary to common opinion, growth inhibition of cancer cells by antiprogestin MF is not dependent upon expression of classical, nuclear PR.

Dataset Information

Chlamydia inhibits progesterone receptor mRNA expression in SHT-290 cells.

Publications

Chlamydia inhibits progesterone receptor mRNA expression in SHT-290 cells.

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